Long-Lasting Cognitive Abnormalities after COVID-19

[pattismith]

Brain Sciences | Free Full-Text | Long-Lasting Cognitive Abnormalities after COVID-19 (mdpi.com)
2021

Abstract

Considering the mechanisms capable of causing brain alterations in COVID-19, we aimed to study the occurrence of cognitive abnormalities in the months following hospital discharge.

We recruited 38 (aged 22–74 years; 27 males) patients hospitalized for complications of SARS-CoV-2 infection in nonintensive COVID units.

Participants underwent neuropsychological testing about 5 months after hospital discharge.

Of all patients, 42.1% had processing speed deficits, while 26.3% showed delayed verbal recall deficits.

21% presented with deficits in both processing speed and verbal memory.

Bivariate analysis revealed a positive correlation between the lowest arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2) (P/F) ratio during hospitalization and verbal memory consolidation performance (SRT-LTS score, r = 0.404, p = 0.027), as well as a positive correlation between SpO2 levels upon hospital arrival and delayed verbal recall performance (SRT-D score, rs = 0.373, p = 0.042).

Acute respiratory distress syndrome (ARDS) during hospitalization was associated with worse verbal memory performance

Cognitive abnormalities can frequently be found in COVID-19 patients 5 months after hospital discharge. Increased fatigability, deficits of concentration and memory, and overall decreased cognitive speed months after hospital discharge can interfere with work and daily activities.

 

[SWAlexander]

42.1% had processing speed deficits,

This was me in 2021. I could not learn (learning delay) or remember (memory delay) new acronyms.
Now it is better but I still have to check if I used the right abbreviation.
I´m convinced it has to do with brain inflammation. The same memory learning and memory deficiency occurred after I had sepsis in 2016.

 

[pattismith]

@SWAlexander ,

In this study
Article - Where Exactly does ME/CFS Research Stand in 2021? Dr. Komaroff Explains | Phoenix Rising ME/CFS Forums

they make a link between enlarged perivascular spaces and processing speed.

The enlarged perivascular spaces may be a result of affected microvascular and blood flow...

 

[Consul]

There is a big study going on in mecfs and fm on neurovascular coupling.

https://neurosciencenews.com/csf-fibromyalgia-neuroimaging-22051/

Quote
The brain accounts for 20% of total body energy consumption but has limited or no energy reservoir. Normal function relies critically on the timely matching of local blood flow to neural energy demand.The researchers believe abnormalities in this process, known as neurovascular coupling, is responsible.

 

[pattismith]

@Consul

I am interested in this neurovascular hypothesis, it makes the Guanfacine trial interesting as Guanfacine is believed to increase regional cerebral blood flow (rCBF) in the frontal lobe

Clinical experience with the α2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in “Long-COVID19” | Phoenix Rising ME/CFS Forums

The Effects of an Alpha-2 Adrenergic Agonist, Guanfacine, on rCBF in Human Cortex in Normal Controls and Subjects with Focal Epilepsy | Neuropsychopharmacology (nature.com)

A wide area of increased rCBF was seen in the frontal lobe, maximal at the central region, following guanfacine in controls and subjects with TLE/Temporal Lobe Epilepsy.
Smaller areas of decrease in rCBF were seen in the posterior temporal-occipital cortex. In the FLE group a decrease in rCBF was seen in the dorsal prefrontal cortex on the epileptogenic side with only small increases seen in the mid- to anterior temporal perisylvian areas.

 

[SWAlexander]

affected microvascular and blood flow

That's a real possibility since I also had thrombosis and APS at the time. Now, after heparin treatments, my memory is better.

 

[Consul]

@Consul

I am interested in this neurovascular hypothesis, it makes the Guanfacine trial interesting as Guanfacine is believed to increase regional cerebral blood flow (rCBF) in the frontal lobe

Maybe cerebral blood flow is also why Rexulti and Abilify helps some patients as well? If you look under the Pharmacology tab on wiki for Rexulti this drug is messing with loads of receptors for adrenergic and muscarinic ligands. And for Abilify it is mentioned some indications that it has some effect on these things as well.

Cerebrovascular blood flow appears to be very complicated though, much more complicated than peripheral blood flow. Dont know much about any of them tbh.

But maybe this is why these drugs work instead of the neuroinflammation inhibitor explanation.

 

[SWAlexander]

Cerebrovascular blood flow appears to be very complicated

Sorry to jump in your dialog. Abilify will not work in all cases.

Abilify Side Effects: https://www.drugwatch.com/abilify/s...syndrome is a,of the autonomic nervous system.

According to: https://www.aans.org/en/Patients/Ne...ions in blood flow may,and may cause a stroke.

Restrictions in blood flow may occur from vessel narrowing (stenosis), clot formation (thrombosis), blockage (embolism) or blood vessel rupture (hemorrhage). Lack of sufficient blood flow (ischemia) affects brain tissue and may cause a stroke.

 

[SWAlexander]

Nebivolol: an effective option against long-lasting dyspnoea following COVID-19 pneumonia - a pivotal double-blind, cross-over controlled study
https://pubmed.ncbi.nlm.nih.gov/36636645/
Abstract

Background: Pulmonary microvascular occlusions can aggravate SARS-CoV-2 pneumonia and result in a variable decrease in capillary blood volume (Vc). Dyspnoea may persist for several weeks after hospital discharge in many patients who have "radiologically recovered" from COVID-19 pneumonia. Dyspnoea is frequently "unexplained" in these cases because abnormalities in lung vasculature are understudied. Furthermore, even when they are identified, therapeutic options are still lacking in clinical practice, with nitric oxide (NO) supplementation being used only for severe respiratory failure in the hospital setting. Nebivolol is the only selective β1 adrenoceptor antagonist capable of inducing nitric oxide-mediated vasodilation by stimulating endothelial NO synthase via β3 agonism. The purpose of this study was to compare the effect of nebivolol versus placebo in patients who had low Vc and complained of dyspnoea for several weeks after COVID-19 pneumonia.

 

[Consul]

Sorry to jump in your dialog. Abilify will not work in all cases.

Abilify Side Effects: https://www.drugwatch.com/abilify/s...syndrome is a,of the autonomic nervous system.

According to: https://www.aans.org/en/Patients/Ne...ions in blood flow may,and may cause a stroke.

Restrictions in blood flow may occur from vessel narrowing (stenosis), clot formation (thrombosis), blockage (embolism) or blood vessel rupture (hemorrhage). Lack of sufficient blood flow (ischemia) affects brain tissue and may cause a stroke.

Lack of sufficient blood flow may cause a stroke.

Stroke is not associated with mecfs so maybe that goes against this idea.

 

[Consul]

Those factors mentioned might just be extremes though. The problem in mecfs might just be lowered amounts of NO or some other dilators produced by the neurons and astrocytes.

 

[pattismith]

Maybe cerebral blood flow is also why Rexulti and Abilify helps some patients as well?

maybe yes...or maybe not. I couldn't say!

But maybe this is why these drugs work instead of the neuroinflammation inhibitor explanation.

Maybe...But inflammation is also a factor affecting brain blood flow...
for example, vascular inflammation produces vascular insuline resistance and reduce ability to relax/dilate.

Also recent articles showed a link between microglia and brain blood flow!

Microglia are brain resident immune cells with multiple functions. However, little is known about microglia-vascular interactions. In a recent paper published in Nature Communications, Bisht et al. identify a signalling mechanism that attracts and maintains microglia at the capillary wall. Moreover, they show that microglia regulate capillary vascular tone, playing a more significant role in blood flow regulation than previously thought

.

Microglia have a grip on brain microvasculature | Nature Communications

Here, we identify microglia as important modulators of CBF both under physiological conditions and during hypoperfusion.

Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actions | Journal of Experimental Medicine | Rockefeller University Press (rupress.org)

 

[Consul]

@pattismith Im thinking that its a bit odd that the meds that work for mecfs arent the ones that are specialized for neuroinflammation but rather these other drugs that also possibly might be doing other things like regulating brain blood flow. Basically i think there are other drugs that are specialized for neuroinflammation but nobody is talking about those for some reason.

That said i think Jarred Younger didnt find any brain perfusion problems in mecfs. I think he mentioned this in one of his vids, but its been a while so i might not remember correctly.

 

[pattismith]

@pattismith Im thinking that its a bit odd that the meds that work for mecfs arent the ones that are specialized for neuroinflammation but rather these other drugs that also possibly might be doing other things like regulating brain blood flow. Basically i think there are other drugs that are specialized for neuroinflammation but nobody is talking about those for some reason.

That said i think Jarred Younger didnt find any brain perfusion problems in mecfs. I think he mentioned this in one of his vids, but its been a while so i might not remember correctly.

Yesterday and today I took intranasal Telmisartan (AT1R blocker that crosses the BBB, increases brain blood flow, (and also activates PPAR gamma and is neuroprotective) and I felt quickly much better! That said, I don't know if I have ME

 

[Consul]

Yesterday and today I took intranasal Telmisartan (AT1R blocker that crosses the BBB, increases brain blood flow, (and also activates PPAR gamma and is neuroprotective) and I felt quickly much better! That said, I don't know if I have ME

Lucky you! Do you sometimes experience PEM?

 

[pattismith]

Lucky you! Do you sometimes experience PEM?

I used to have PEM when I was strongly iron deficient.
Now that I repleted my iron stores and that I take methylphenidate, I no longer suffer with PEM. but I still suffer from headache, attention deficit and brain fog.

Methylphenidate induces vasoconstriction, and I suppose that could be a reason why I can't tolerate slow released forms, or high dosage. That's why I was looking for an appropriate drug that could protect me against MP side effects.

I don't have Guanfacine so I decided to give a try with Telmisartan. I have high GPCR antibodies against AT1R (and ETAR), so this choice makes sense to me. I wish this good effect will last a bit

 

[hapl808]

I wonder if guanfacine has a good potential for longer term benefits. Methylphenidate seems like it would be a crutch that might help in the short term, but is there anyone who has gotten long term benefits from it without worsening their crashes? And I still wonder about low dose Abilify - haven't tried that either.